Both acute and chronic pain are associated with an incalculable toll in human suffering and present a significant economic problem. One of the major challenges in treating pain arises from the tremendous inter- individual variation in subjective reports of pain. Individuals with similar injuries will frequently report vastly differet experiences of pain. Such individual differences often result in inadequate treatment due to concerns about the validity or veracity of subjective reports of pain. Despite the profound clinica significance of individual differences in pain, remarkably little is known about the basic brain mechanisms that support such differences. Portions of this inter-individual variation in subjective reports of pain may be due to physical factors such as brain connectivity. Other components arise from psychological disposition and may involve factors such as cognitive control, impulsivity, depression, and anxiety. Finally, demographic variables such as sex and ethnicity may also substantially contribute to individual differences in pain sensitivity. Surprisingly littl is known about the brain mechanisms by which these factors influence the construction of the pain experience at the level of a single individual. Thus, the fundamental aim of the proposed research is to delineate the brain mechanisms that give rise to individual differences in pain sensitivity. We will acquire both functional and structural MRI data from a large number (392) of volunteers. Recruitment will be designed to obtain a true community sample in order to facilitate generalizability of findings. As such, this research will involve individuals of differing socio-economic levels, obese individuals, individuals with active depression and anxiety, as well as those in excellent physical and mental health. Participants will also undergo extensive sensory testing and psychological evaluation in order to fully characterize their pain phenotype. Multiple regression statistical analyses will be used to identify brain regions related to inter-individual differences in sensitivity in both structural and functional neuroimaging data. Techniques such as psychophysiological interaction analyses will be used to test hypotheses about the influence of functional connectivity on pain sensitivity. The identification of brain mechanisms that support individual differences in pain sensitivity will contribute substantially to our basic understandingof brain mechanisms of pain and will critically evaluate our existing notions that every individual processes nociceptive information in the same way. The results from the proposed studies will provide a solid rationale for the development of individualized pain treatment strategies.